Contact PD/PI: He, Ka Studies indicate that a satisfactory content of some micronutrients within the cells maintains several immune functions, anti-inflammatory and anti-oxidant activities, which together may play a pivotal role in reducing the effects of aging. In contrast, although the underlying mechanisms are unclear, studies have linked some heavy metal exposure to cognitive decline, which is clearly associated with aging. Despite this, there remains a critical gap in the literature on how trace minerals, both nutritious elements and heavy metals, affect cognitive health. In particular, data directly relating trace mineral levels to cognitive decline are lacking. In addition, leukocyte telomere length (TL) has been consistently shown to have a direct relation with mortality and aging- related diseases in epidemiological studies, and is thus considered to be a biomarker of aging. TL has also been linked to cognitive function in different populations. Although TL is heritable, it can be modified by a host of environmental variables. Thus, identifying modifiable factors that may slow or prevent TL attrition would certainly have a major public health impact, as possible interventions are likely to be most effective during the early stages of preclinical disease. The overall objective of this project is to examine the longitudinal associations between trace mineral levels and cognitive decline and TL. Specifically, we will examine the trace mineral concentrations measured in urine or serum in relation to the trajectory of cognitive decline, as well as TL, and telomere attrition in a sub-cohort (n=2,391) of participants randomly selected from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study, an ongoing US national population-based, general population cohort of 30,239 African American and Caucasian adults, aged 45 and older at baseline (2003-2007). The proposed study will help to identify at-risk Americans for cognitive decline and/or the consequences of aging. For nutritious minerals, information generated from this study will be useful for future interventions to maintain a homeostasis of micronutrients in relation to healthy aging; and for the toxic ones at low-to-moderate exposure level, knowledge gained will serve as a scientific foundation for remediation and prevention strategies to improve cognitive health or slow down the consequences of aging. Project Summary/Abstract Page 7